Table 2.

Summary of key knowledge gaps and recommendations

Main gaps in knowledge	Future pre-clinical study priorites
Establishing dosing regimes for combinatorial treatments, e.g. SRS/ WBRT with ICT	Including radiotherapy and other regimens in pre-clinical studies
Limited permeability and heterogenous nature of BTB and BBB	Novel BTB/BBB disruption approaches
Treatment naive pre-clinical models do not reflect the majority of BrM patients	Including radiotherapy and other regimens in pre-clinical studies
Limitations in cancer cell lines used most often in BrM pre-clinical studies	Effective utilization of avaliable patient data sets and novel technologies
Sparse inclusion of health span metrics and neurological function in pre-clinical studies	Expanding treatment efficacy endpoints to include behavioral and health metrics
Low sensitivity of imaging modalities to detect o early BrM lesions	Improving imaging resolutions for enhanced sensitivity
Lack of specific molecular targets, mechanisms, and role of the hetereogenous brain TME	Mechanistic study designs informed by single cell analysis of BrM and BrM TME