standoffs

Pretty much, those holes are for you to screw your mobo into the standoffs, which hold the board up from below.

Some cases have built-in standoffs in the standard positions, for others you have to screw the little brass hex standoffs into the holes in the case.
 
Every hole in your case tray that matches a motherboard hole should be used to mount the motherboard.
Every hole in your case tray that does not match a motherboard hole should be left empty, avoiding any electrical shorts to ground.
 
so long as there's nothing plugged into it, yeah.

If the screws arent gripping the motherboard, get shorter screws 😉 Or your standoffs might be stripped or mis-threaded.-