Brain metastases

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Brain metastases are deposits from a cancer arising elsewhere. Haematogenous spread often seeds the grey-white junction or other vascular territories, and lesions can be solitary, oligometastatic or numerous. Oedema may create more symptoms than the tumour volume itself. Melanoma, renal-cell carcinoma and some other metastases can bleed. The primary may be known, newly discovered during staging or initially occult.

Presentation includes focal deficit, seizure, headache, cognitive or personality change, gait disturbance and raised intracranial pressure. A person with cancer may still have stroke, infection, treatment toxicity or a primary brain tumour, so the diagnosis should not be assumed from history alone. Conversely, an apparently controlled extracranial cancer does not rule out intracranial relapse. Acute neurological decline demands emergency imaging for haemorrhage, hydrocephalus and mass effect.

Treatment integrates intracranial and systemic disease. Surgery is especially useful for a large accessible lesion causing mass effect, when tissue is needed or when one dominant lesion drives symptoms. Stereotactic radiosurgery or stereotactic radiotherapy provides focal control for selected intact lesions or resection cavities. Whole-brain radiotherapy treats diffuse intracranial burden but risks cognitive toxicity and is not an automatic default. Some molecularly selected cancers respond to CNS-active systemic therapy. NICE NG99 and ASCO-SNO-ASTRO both require multidisciplinary selection rather than a rigid rule based only on number.

Key points

Brain metastases are secondary tumours arriving mainly by the bloodstream; common primaries include lung, breast, melanoma, renal and gastrointestinal cancers, but any cancer history must be interpreted with the scan and current pathology.
Symptoms reflect lesion location, number, haemorrhage, oedema and CSF obstruction; a patient can have a solitary dominant lesion or numerous small metastases.
Symptomatic brain metastases should receive local therapy when appropriate regardless of systemic therapy; urgent mass effect needs immediate neurosurgical and oncological assessment.
Contrast-enhanced structural MRI defines lesion number, volume and location more accurately than emergency non-contrast CT, while extracranial staging and tumour molecular profile show whether systemic disease is controllable and targetable.
Choose treatment using performance status, extracranial and leptomeningeal disease, primary site and molecular profile, lesion number and total volume, location, resection cavity, life expectancy and patient preferences.
Surgery, stereotactic radiosurgery or radiotherapy, systemic anticancer therapy, whole-brain radiotherapy and supportive care have different goals and harms; none is selected from lesion count alone.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Haematogenous spread

Circulating tumour cells cross cerebral microvasculature and seed brain parenchyma, often near grey-white junctions or other vascular watershed interfaces.

Primary tumour biology

Lung, breast, melanoma, renal and gastrointestinal cancers commonly metastasise to brain, but molecular subtype and treatment history alter individual probability.

Leptomeningeal dissemination

Tumour can spread through CSF and coat meninges or nerve roots, producing multifocal neuraxial symptoms distinct from isolated parenchymal deposits.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Vasogenic oedema
Disrupted tumour vessels allow plasma into extracellular white matter, expanding tissue volume and causing deficit or pressure out of proportion to lesion diameter.
2
Local network disruption
Deposits compress or infiltrate motor, language, visual, cerebellar and cognitive networks; eloquent location can make a small lesion highly symptomatic.
3
Haemorrhagic transformation
Fragile tumour vasculature can bleed, especially in selected histologies, creating abrupt deficit and a combined oncological and haemorrhagic emergency.
4
CSF obstruction
Posterior-fossa or ventricular lesions can block CSF pathways and produce acute hydrocephalus, drowsiness and herniation before extracranial staging is complete.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Focal neurological loss

Map weakness, sensory change, language disturbance, visual-field loss, neglect and coordination deficits. The dominant lesion may not be the largest if its location involves eloquent cortex or a narrow CSF pathway.

Seizure and recoveryRed flag

Characterise focal onset, duration, recurrence and residual deficit. Ongoing seizure or incomplete recovery requires emergency treatment and imaging, while a recovered first seizure still needs prompt structural evaluation.

Pressure and haemorrhageRed flag

Progressive headache, vomiting, drowsiness, papilloedema or pupil change can reflect oedema or hydrocephalus; abrupt severe symptoms may indicate intratumoural haemorrhage.

Cancer and treatment history

Establish primary site, histology, molecular profile, previous therapies, response, current systemic burden and immunosuppression. Old pathology may need review because modern targeted options depend on current biology.

Leptomeningeal pattern

Multifocal cranial neuropathies, radicular pain, cauda-equina symptoms, encephalopathy or deficits at several neuraxial levels suggest meningeal dissemination rather than isolated parenchymal deposits.

Function and goals

Assess performance, cognition, frailty, independence and what outcomes matter to the patient. Treatment burden can outweigh local-control benefit when systemic disease or functional decline dominates prognosis.

Red flags requiring action

New focal deficit, seizure, cognitive change, gait dysfunction or persistent headache in a person with current or previous cancer.
Falling consciousness, pupil change, repeated vomiting or rapid motor decline indicating mass effect or acute haemorrhage.
A solitary or dominant large lesion with oedema and mass effect that may benefit from surgical decompression and tissue diagnosis.
New neurological symptoms during surveillance after treatment, which require clinical review and appropriate imaging rather than waiting for the next scheduled visit.
Back pain, radicular symptoms, sphincter change or limb weakness suggesting separate spinal metastatic disease or cord compression.
Leptomeningeal symptoms such as multifocal cranial neuropathies, radicular pain or widespread neurological deficits, which follow a different investigation and treatment pathway.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Urgent non-contrast CT headFirst step
Why
Detect haemorrhage, hydrocephalus, major oedema and mass effect rapidly in an acutely deteriorating patient.
Interpretation and limitations
CT can reveal a dangerous lesion needing immediate action but undercounts small metastases and cannot fully plan focal therapy. Stabilisation and specialist involvement continue even if systemic staging is incomplete.
02
Contrast-enhanced structural MRI brain
Why
Define the number, volume, location and treatment relationships of suspected brain metastases.
Interpretation and limitations
NICE specifies T2, FLAIR, DWI and T1 pre- and post-contrast volume sequences. MRI better detects small lesions; a single ring-enhancing lesion still has abscess, primary tumour and inflammatory differentials.
03
Extracranial staging
Why
Establish primary tumour, systemic disease control, competing prognosis and whether a local intracranial strategy is proportionate.
Interpretation and limitations
CT, PET or site-specific tests follow the suspected primary and prior cancer. Staging informs rather than delays emergency decompression of a life-threatening dominant lesion.
04
Tissue diagnosis and molecular profile
Why
Confirm origin when uncertain and identify biomarkers that predict CNS-active systemic therapy.
Interpretation and limitations
Resection or biopsy is particularly valuable for unknown primary, long interval, discordant imaging or when pathology will alter treatment. Previously stored tissue may be sufficient in a typical known-cancer pattern.
05
Advanced MRI for suspected recurrence
Why
Help distinguish recurrent tumour from treatment effect when standard follow-up imaging is unclear and the result would change management.
Interpretation and limitations
Perfusion, spectroscopy and serial evolution can refine probability, but radionecrosis and progression may overlap. Tissue or interval review is sometimes still required.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Primary glioma

An infiltrative solitary lesion may be a primary diffuse glioma. Imaging patterns overlap, and tissue is valuable when diagnosis changes therapy.

Brain abscess

Ring enhancement with fever, infection source or diffusion restriction suggests abscess, but immunosuppressed patients may lack systemic signs and need urgent specialist review.

Treatment effect

Radiation necrosis and pseudoprogression can mimic recurrent metastasis after local therapy. Timing, advanced imaging, serial change and sometimes tissue are needed.

Vascular disease

Stroke and haemorrhage commonly occur in cancer patients and can resemble metastatic progression. Sudden onset demands the acute vascular pathway alongside oncological context.

Inflammatory disease

Demyelination, granulomatous disease and treatment-related immune inflammation can enhance and cause focal deficits; medication timing and imaging distribution refine the differential.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01Symptomatic local-therapy pathwayLarge solitary metastasis with mass effectFirst stepA patient with cancer develops progressive hemiparesis and MRI shows one accessible large lesion with substantial oedema.

1Assess emergency pressure signs, seizure, function and reversibility, and involve neurosurgery, radiation oncology and the primary-tumour team promptly.
2Review extracranial control, performance status, lesion location and operative risk while treating acute symptoms; symptomatic disease should not wait for systemic therapy alone.
3Consider surgical resection when rapid decompression and tissue diagnosis offer benefit, followed by a resection-cavity radiation strategy where appropriate.
4If surgery is unsuitable, choose stereotactic or other radiotherapy according to lesion size, volume, location, number and normal-tissue constraints rather than number alone.
5Verify neurological recovery, pathology and molecular findings, postoperative imaging, systemic plan and a person-specific follow-up schedule at MDT.

02Systemic-integration pathwayMultiple metastases without acute mass effectMRI shows several lesions in a person who is stable enough for full multidisciplinary selection.

1Confirm intracranial burden and symptoms, assess performance, extracranial and leptomeningeal disease, life expectancy and patient priorities.
2Determine whether the primary tumour has a CNS-active systemic option and whether deferring local therapy is explicitly supported for that disease and clinical state.
3Select focal stereotactic treatment, whole-brain radiotherapy, systemic therapy, combined treatment or supportive care by expected benefit, toxicity and feasibility.
4Explain cognitive, functional and logistical trade-offs and document why the selected strategy fits both intracranial and systemic goals.

03Uncertain-diagnosis pathwaySolitary lesion with no known primaryImaging shows a solitary enhancing brain lesion without a confirmed extracranial malignancy.

1Keep metastasis, primary brain tumour, abscess and inflammatory disease in the differential and obtain contrast MRI with targeted systemic assessment.
2Discuss resection or biopsy when tissue will establish origin and direct therapy, balancing diagnostic yield against anatomical risk.
3Avoid labelling the lesion metastatic or starting a tumour-specific systemic regimen without adequate pathological or multidisciplinary support.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Intracranial pressure crisis

Oedema, haemorrhage or hydrocephalus can cause falling consciousness and herniation, requiring immediate physiological stabilisation and local source control.

Seizure and injury

Cortical irritation causes focal or generalised seizures, which can impair driving, independence and treatment adherence and occasionally progress to status epilepticus.

Cognitive decline

Tumour burden, whole-brain radiation, systemic therapy, seizures and medicines can impair memory and executive function, creating major caregiver and consent needs.

Treatment toxicity

Surgery, stereotactic radiation and systemic therapy can cause deficit, radionecrosis, wound problems or systemic adverse effects; benefit must be weighed against prognosis.

Systemic progression

Extracranial cancer often determines survival and treatment tolerance. Intracranial decisions must remain coordinated with the primary tumour strategy and palliative priorities.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

NICE recommends regular clinical review that assesses physical, psychological and cognitive wellbeing, with frequency individualised to disease and treatment context.
Base imaging intervals on extracranial disease, life expectancy, primary cancer, available treatment options and the person’s preferences rather than one universal schedule.
Use standard structural MRI to assess recurrence or progression unless contraindicated, and consider advanced techniques when standard findings are equivocal and early clarification would help.
Arrange clinical review with appropriate imaging for new or changing neurological symptoms at any time, regardless of the planned surveillance date.
Monitor neurological function, seizure burden, steroid effects when used, cognition, rehabilitation needs and systemic-treatment toxicity alongside tumour measurements.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Volume beats count alone

Number matters, but total tumour volume, lesion size, location and normal-brain dose can be more decisive for surgery or stereotactic feasibility than a simple numerical cut-off.

Tissue can reopen options

A new intracranial lesion may have a changed molecular profile or a different diagnosis. Resection can simultaneously decompress, establish origin and enable current biomarker testing.

Systemic control matters

Excellent local brain control may offer little benefit when extracranial disease is rapidly fatal, while durable systemic control can justify aggressive treatment of limited intracranial disease.

Symptoms favour local action

ASCO-SNO-ASTRO recommends local therapy for symptomatic metastases regardless of systemic treatment. Deferral is reserved for specified asymptomatic molecular and treatment contexts.

Leptomeningeal disease differs

Diffuse meningeal spread changes prognosis, investigation and treatment; it should not be compressed into a parenchymal lesion-count algorithm.

11Common pitfallsFrequent interpretation and management errors.

01
Assuming every new neurological symptom in a cancer patient is metastatic rather than considering stroke, infection, toxicity and primary CNS disease.
02
Delaying local treatment of symptomatic mass effect because a systemic drug is planned.
03
Choosing whole-brain radiotherapy automatically from lesion count without considering total volume, focal options, cognition and systemic prognosis.
04
Searching exhaustively for an occult primary before controlling life-threatening intracranial pressure or obtaining useful tissue from an accessible lesion.
05
Using a fixed follow-up schedule without considering extracranial disease, available salvage options, preferences and new symptoms.

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