Table 1 Eligibility criteria - inclusions and exclusions

• One to three (1-3) intracranial metastases on MRI from melanoma, all locally treated with either surgical excision and/or stereotactic irradiation. (It will be assumed that the metastases are melanoma if the patient has documented histological or radiological concurrent extracranial disease that has already categorised the patient as stage IV). If the cerebral lesion(s) is/are the first presentation of stage IV disease, then one metastasis must be histologically proven to be melanoma for the patient to be included in the study.

• Life expectancy of at least 6 months.

• Aged 18 years or older.

• WBRT must begin within 8 weeks of completion of local treatment and within 4 weeks of randomisation.

• Able to have an MRI brain scan with contrast enhancement. Estimated glomerular filtration rate (eGFR) is adequate at the discretion of the radiologist and capable of having gadolinium-containing contrast medium for MRI (as per practice guidelines).

• Localised treatment of all brain metastases no more than 6 weeks prior to randomisation.

• An ECOG performance status of 0, 1 or 2 at randomisation.

• CT scan of chest, abdomen and pelvis within 12 weeks of randomisation.

• Serum lactate dehydrogenase (LDH) must be ≤ 2 times upper limit of the participating centre's reference range.

• Able to provide written informed consent.

• Any untreated intracranial disease.

• Any previous intracranial treatment (surgical excision and/or stereotactic irradiation treatment and/or WBRT) prior to this diagnosis of intracranial melanoma.

• Evidence of leptomeningeal disease on pre-local treatment MRI scan.

• Patients with prior cancers, except: those diagnosed more than five years ago with no evidence of disease recurrence within this time; successfully treated basal cell and squamous cell skin carcinoma; or carcinoma in-situ of the cervix.

• A medical or psychiatric condition that compromises ability to give informed consent or complete the protocol.

• Positive urine pregnancy test for women of childbearing potential.