Table 1 Eligibility Criteria

• 21–80 years old patients

• Radiological confirmed brain metastases (4–25 lesions)

• Histologically proven malignancy

• ECOG performance status ≤2

• Maximum lesion or cavity size ≤5 cm

 o For patients with large (≥3 cm) lesions, a neurosurgical consult is recommended due to the increased risk of cerebral oedema

 o If brain surgery or other invasive procedures are performed, the treatment should begin at least 2-weeks post-procedure

• Life expectancy of at least 6 months

• Negative serum pregnancy test within 14 days prior to registration for women of childbearing potential

• Women of childbearing potential and male participants who are sexually active must agree to use a medically effective means of birth control throughout protocol treatment

• Not suitable for or does not want SRS

• Agrees to be randomised to either HA-WBRT or HA-SIB-WBRT

• Prior whole brain radiotherapy.

o Prior SRS is not an exclusion. Details of treatment must be recorded.

• Diffuse leptomeningeal disease

• Extensive extracranial disease, not controlled by systemic treatment

• Major medical or psychiatric illness, which in the investigator’s opinion would interfere with the completion of therapy and follow up

• Dementia, ongoing psychotic episodes or moderate-severe depression (PHQ-9).

• Recent stroke in the past 3 months

• Symptomatic brain metastases limiting ADLs

• Rapid progression of brain lesion

• Patients unable to give informed consent

• Total tumour planning target volume (PTV) > 60 cc

• Radiological evidence of hydrocephalus

• Contraindication to Gadolinium contrast-enhanced MRI brain

• Patients with diagnoses of small cell carcinoma, lymphoma or primary brain tumour